Induction of Drug Metabolism-Related Enzymes by Methylcholanthrene and Phenobarbital in Transgenic Mice Carrying Human Prototype c-Ha-ras Gene and Their Wild Type Littermates

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概要

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• Transgenic mice hemizygously carrying human c-Ha-ras proto-oncogene, Tg-rasH2 show very sensitive and facilitated carcinogenicity to various carcinogens. In this study, activities of certain enzymes related to drug metabolism and energy metabolism were measured in microsome and cytosol fractions of livers of Tg-rasH2 mice and their wild type littermates with both sexes treated with 3-methylcholanthrene (MC) and phenobarbital (PB). Aminopyrine N-demethylase activities increased significantly in livers of all mice treated with PB. MC and PB treatments induced significant increases in activities of UDP-glucuronosyltransferase and S-adenosyl homocysteinase compared to those in the non-treated groups in microsome fractions from all mice. In cytosol fractions of livers of all mice, glutathione S-transferase activity was significantly induced in the PB treated groups. There were no significant differences in activities of lactate dehydrogenase, glucose 6-phosphate dehydrogenase, pyruvate kinase and glucose 6-phosphatase related to energy metabolism in livers and kidneys among all mice. Tg-rasH2 mice showed stable activities of enzymes related to drug detoxication and energy metabolism similar to those of non-transgenic mice. These results suggest that the human c-Ha-ras transgene may not affect drug metabolism-related enzymes, and the facilitated carcinogenic response in the Tg-rasH2 mouse is not due to these enzymatic disorders.

• 社団法人　日本実験動物学会の論文

著者

• Oishi Yumiko

  Department Of Cardiology The University Of Tokyo

• UEYAMA Yoshito

  Department of Pathology, School of Medicine, Tokai University

• Ohishi Yumiko

  東京大学 医学系研究科循環器内科

• 高倉 彰

  財団法人実験動物中央研究所

• Takakura Akira

  実験動物中央研究所 Iclasモニタリングセンター

• Ueyama Y

  Dep. Of Pathology Tokai Univ. School Of Medicine

• Ueyama Y

  Tokai Univ. School Of Medicine Kanagawa Jpn

• Ueyama Y

  Tokai Univ. School Of Medicine Isehara‐shi Jpn

• Ueyama Yoshito

  Department Of Pathology Tokai University School Of Medicine

• Tamaoki N

  Central Inst. For Experimental Animals

• Tamaki Norikazu

  Central Institute For Experimental Animals

• Tani N

  The 6th Department Of Internal Medicine School Of Medicine Tokai University

• OHNISHI Yasuyuki

  Central Institute for Experimental Animals

• URANO Kohji

  Central Institute for Experimental Animals

• Usui Toshimi

  Central Institute for Experimental Animals

• Ueyama Yoshito

  Department Of Pathology School Of Medicine Tokai University

• ARAI Toshiro

  Division of Veterinary Biochemistry

• KOSHIRAKAWA Miho

  Division of Veterinary Biochemistry

• HORII Noriko

  Division of Veterinary Biochemistry

• NAKAJO Shinjiro

  Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University

• TAMAOKI Norikazu

  Central Institute for Experimental Animals

• Hoya Naoko

  Central Inst. For Experimental Animals

• Tamaoki Norikazu

  Central Inst. For Experimental Animals

• Ohnishi Yasuyuki

  Central Inst. For Experimental Animals

• Arai T

  Dep. Of Veterinary Biochemistry Fac. Of Veterinary Medicine Nippon Veterinary And Animal Sci. Univ.

• Umezawa Y

  Department Of Dermatology Tokai University School Of Medicine

• Nakajo Shinjiro

  Division Of Veterinary Pharmacology Nippon Veterinary And Animal Science University

• Ueyama Yoshihito

  Department Of Pathology Tokai University School Of Medicine

• UEYAMA Yoshito

  Department of Dermatology, Division of Specialized Clinical Science, Tokai University School of Medicine

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